Back to resultsLanthanum Carbonate (Fosrenol®) to Reduce Oxalate Excretion in Patients With Secondary Hyperoxaluria and Nephrolithiasis (LaCa)
Primary Purpose
Secondary Hyperoxaluria, Nephrolithiasis
Status
Unknown status
Phase
Phase 3
Locations
Belgium
Study Type
Interventional
Intervention
Lanthanum Carbonate
Sponsored by
About this trial
This is an interventional treatment trial for Secondary Hyperoxaluria focused on measuring Nephrolithiasis, Urolithiasis, Secondary Hyperoxaluria, Hyperoxaluria, Lanthanum Carbonate, Phosphate Binder
Eligibility Criteria
Inclusion Criteria:
- able to give written informed consenct
- hyperoxaluria (defined as urinary oxalate > 45 mg/24 hours), demonstrated on 24-hour urine collection within 18 months prior to baseline visit
- history of nephrolithiasis eGFR > 60 mL/min/1.73m² (CKD-EPI formula)
Exclusion Criteria:
- primary hyperoxaluria, diagnosed by genetic testing
- known allergy to Lanthanum Carbonate
- hypophosphatemia (defined as serum phosphorus < 0.81 mmol/L)
- severe known liver insufficiency of biliary obstruction
- rectocolitis ulcerohaemorraghica, Crohn's disease, bowel obstruction, stomach/duodenal ulceration
- glucose/galactose malabsorption
- severe diarrhea or other gastrointestinal disorder, which might interfere with the ability to absorb oral medication
- pregnancy or breast-feeding
- female participant of childbearing potential unwilling to take efficient contraceptive measures for the duration of the study
- female participant without negative serum or urine pregnancy test
- psychological illness or condition, interfering with the patient's compliance or ability to understand the requirements of the study
- currently participating in another clinical trial
Sites / Locations
- University Hospital BrusselsRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Experimental single arm
Arm Description
Treatment with Lanthanum Carbonate 3 x 250 mg/day with meals during a first 14-day treatment period. Subsequently, treatment with Lanthanum Carbonate 3 x 500 mg/day with meals during a second 14-day treatment period.
Outcomes
Primary Outcome Measures
The mean reduction in urinary oxalate excretion in patients treated with a daily Lanthanum Carbonate dose of 750 mg
Mean reduction in urinary oxalate excretion after the first 14-day treatment period during which patients will be treated with 250 mg Lanthanum Carbonate 3x/day with meals, expressed in mg oxalate/g creatinine.
Secondary Outcome Measures
The incremental reduction in mean urinary oxalate excretion after doubling the dose of Lanthanum Carbonate from 750 mg tot 1500 mg daily
Incremental reduction of mean urinary oxalate excretion after the second 14-day treatment period during which the patients will be treated with 500 mg Lanthanum Carbonate 3x/day with meals, expressed in mg oxalate/g creatinine
The proportion of patients developing severe hypophosphatemia
Severe hypophosphatemia is defined as serum phosphorus < 0.64 mmol/L
The evolution of phosphaturia, evaluated by 24-hour urinary phosphorus excretion
24-hour urinary phosphorus excretion will be expressed in mmol/24 hours
The evolution of phosphaturia, evaluated by urinary phosphorus to creatinine ratio
Urinary phosphorus to creatinine ratio will be expressed in mmol phosphorus/g creatinine
The evolution of phosphaturia, evaluated by fractional excretion of phosphorus
Fractional excretion of phosphorus will be expressed in %, defined as (urinary phosphorus (mmol/L) x serum creatinine (mg/dL) / (serum phosphorus (mmol/L) x urine creatinine (mg/dL))
The proportion of patients developing hypophosphaturia
Hypophosphaturia is defined as urinary phosphorus < 12.9 mmol/24 hours
The evolution of calciuria, evaluated by 24-hour urinary calcium excretion
24-hour urinary calcium excretion will be expressed in mmol/24 hours
The evolution of calciuria, evaluated by urinary calcium to creatinine ratio
Urinary calcium to creatinine ratio will be expressed in mmol calcium/g creatinine
The evolution of calciuria, evaluated by fractional excretion of calcium
Fractional excretion of calcium will be expressed in %, defined as (urinary calcium (mmol/L) x serum creatinine (mg/dL)) / (serum calcium (mmol/L) x urine creatinine (mg/dL))
The evolution of serum Lanthanum levels
Serum Lanthanum levels will be expressed in mcg/L
Adverse events
The number and the proportion of patients experiencing adverse events
Full Information
NCT ID
NCT03346369
First Posted
March 28, 2017
Last Updated
January 7, 2021
Sponsor
Universitair Ziekenhuis Brussel
1. Study Identification
Unique Protocol Identification Number
NCT03346369
Brief Title
Lanthanum Carbonate (Fosrenol®) to Reduce Oxalate Excretion in Patients With Secondary Hyperoxaluria and Nephrolithiasis
Acronym
LaCa
Official Title
Lanthanum Carbonate (Fosrenol®) to Reduce Oxalate Excretion in Patients With Secondary Hyperoxaluria and Nephrolithiasis: a Short-term, Prospective, Open-label, Efficacy and Safety Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Unknown status
Study Start Date
August 18, 2017 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
December 31, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitair Ziekenhuis Brussel
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study investigates the efficacy and the safety of Lanthanum Carbonate for the reduction of urinary oxalate excretion in patients with secondary hyperoxaluria and nephrolithiasis.
Detailed Description
Nephrolithiasis/urolithiasis is a prevalent (overall lifetime risk up to 13% in Western countries) and highly recurrent disease. Secondary hyperoxaluria is a key risk factor for the development of calcium oxalate stones, the most frequent stone type. Currently used therapeutic options in secondary hyperoxaluria have limited efficacy. Recent findings in vitro and in a rat model, provided evidence that Lanthanum Carbonate is an effective oxalate binder. The objective of this study is to investigate whether treatment with Lanthanum Carbonate reduces urinary oxalate excretion in human subjects with secondary hyperoxaluria and nephrolithiasis. By treating the patients with two different doses of Lanthanum Carbonate during two 14-day treatment periods, a dose-response will be evaluated.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Secondary Hyperoxaluria, Nephrolithiasis
Keywords
Nephrolithiasis, Urolithiasis, Secondary Hyperoxaluria, Hyperoxaluria, Lanthanum Carbonate, Phosphate Binder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Model Description
This study investigates the efficacy and the safety of Lanthanum Carbonate for the reduction of urinary oxalate excretion in patients with secondary hyperoxaluria and nephrolithiasis. Patients will be treated during 2 consecutive 14-day treatment periods with a low and a high dose of Lanthanum Carbonate respectively.
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental single arm
Arm Type
Experimental
Arm Description
Treatment with Lanthanum Carbonate 3 x 250 mg/day with meals during a first 14-day treatment period. Subsequently, treatment with Lanthanum Carbonate 3 x 500 mg/day with meals during a second 14-day treatment period.
Intervention Type
Drug
Intervention Name(s)
Lanthanum Carbonate
Intervention Description
Treatment with Lanthanum Carbonate 3 x 250 mg/day with meals during a first 14-day treatment period. Subsequently, treatment with Lanthanum Carbonate 3 x 500 mg/day with meals during a second 14-day treatment period
Primary Outcome Measure Information:
Title
The mean reduction in urinary oxalate excretion in patients treated with a daily Lanthanum Carbonate dose of 750 mg
Description
Mean reduction in urinary oxalate excretion after the first 14-day treatment period during which patients will be treated with 250 mg Lanthanum Carbonate 3x/day with meals, expressed in mg oxalate/g creatinine.
Time Frame
After the first 14-day treatment period
Secondary Outcome Measure Information:
Title
The incremental reduction in mean urinary oxalate excretion after doubling the dose of Lanthanum Carbonate from 750 mg tot 1500 mg daily
Description
Incremental reduction of mean urinary oxalate excretion after the second 14-day treatment period during which the patients will be treated with 500 mg Lanthanum Carbonate 3x/day with meals, expressed in mg oxalate/g creatinine
Time Frame
After the second 14-day treatment period
Title
The proportion of patients developing severe hypophosphatemia
Description
Severe hypophosphatemia is defined as serum phosphorus < 0.64 mmol/L
Time Frame
After the first and second 14-day treatment period
Title
The evolution of phosphaturia, evaluated by 24-hour urinary phosphorus excretion
Description
24-hour urinary phosphorus excretion will be expressed in mmol/24 hours
Time Frame
After the first and second 14-day treatment period
Title
The evolution of phosphaturia, evaluated by urinary phosphorus to creatinine ratio
Description
Urinary phosphorus to creatinine ratio will be expressed in mmol phosphorus/g creatinine
Time Frame
After the first and second 14-day treatment period
Title
The evolution of phosphaturia, evaluated by fractional excretion of phosphorus
Description
Fractional excretion of phosphorus will be expressed in %, defined as (urinary phosphorus (mmol/L) x serum creatinine (mg/dL) / (serum phosphorus (mmol/L) x urine creatinine (mg/dL))
Time Frame
After the first and second 14-day treatment period
Title
The proportion of patients developing hypophosphaturia
Description
Hypophosphaturia is defined as urinary phosphorus < 12.9 mmol/24 hours
Time Frame
After the first and second 14-day treatment period
Title
The evolution of calciuria, evaluated by 24-hour urinary calcium excretion
Description
24-hour urinary calcium excretion will be expressed in mmol/24 hours
Time Frame
After the first and second 14-day treatment period
Title
The evolution of calciuria, evaluated by urinary calcium to creatinine ratio
Description
Urinary calcium to creatinine ratio will be expressed in mmol calcium/g creatinine
Time Frame
After the first and second 14-day treatment period
Title
The evolution of calciuria, evaluated by fractional excretion of calcium
Description
Fractional excretion of calcium will be expressed in %, defined as (urinary calcium (mmol/L) x serum creatinine (mg/dL)) / (serum calcium (mmol/L) x urine creatinine (mg/dL))
Time Frame
After the first and second 14-day treatment period
Title
The evolution of serum Lanthanum levels
Description
Serum Lanthanum levels will be expressed in mcg/L
Time Frame
After the first and second 14-day treatment period
Title
Adverse events
Description
The number and the proportion of patients experiencing adverse events
Time Frame
After the first and second 14-day treatment period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
able to give written informed consenct
hyperoxaluria (defined as urinary oxalate > 45 mg/24 hours), demonstrated on 24-hour urine collection within 18 months prior to baseline visit
history of nephrolithiasis eGFR > 60 mL/min/1.73m² (CKD-EPI formula)
Exclusion Criteria:
primary hyperoxaluria, diagnosed by genetic testing
known allergy to Lanthanum Carbonate
hypophosphatemia (defined as serum phosphorus < 0.81 mmol/L)
severe known liver insufficiency of biliary obstruction
rectocolitis ulcerohaemorraghica, Crohn's disease, bowel obstruction, stomach/duodenal ulceration
glucose/galactose malabsorption
severe diarrhea or other gastrointestinal disorder, which might interfere with the ability to absorb oral medication
pregnancy or breast-feeding
female participant of childbearing potential unwilling to take efficient contraceptive measures for the duration of the study
female participant without negative serum or urine pregnancy test
psychological illness or condition, interfering with the patient's compliance or ability to understand the requirements of the study
currently participating in another clinical trial
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Celine Olbrechts, Study Coordinator
Phone
+32 (0)2 477 62 24
Email
Celine.Olbrechts@uzbrussel.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christian Tielemans, MD, PhD
Organizational Affiliation
Department of Nephrology, University Hospital Brussels
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Brussels
City
Brussels
ZIP/Postal Code
1090
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Els Van de Perre, MD
Phone
+32 (2) 477 60 55
First Name & Middle Initial & Last Name & Degree
Celine Olbrechts
Phone
+32 (2) 477 62 24
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Lanthanum Carbonate (Fosrenol®) to Reduce Oxalate Excretion in Patients With Secondary Hyperoxaluria and Nephrolithiasis
We'll reach out to this number within 24 hrs